A mechanism of action to account for the antitumor activity and cytotoxicity of certain drugs was proposed which was termed bio- oxidative alkylation. This hypothesis has led to the design of new potential antitumor agents in the ellipticine and olivacine series. The mechanism of action was partially confirmed in the case of hycanthone and the precise mode of activity of it and an analog of ellipticine will be studied further. It is suggested that these drugs are involved in the irreversible interaction with the mammalian DNA Topoisomerase II-DNA complex and that this is the cytotoxic event. Experiments are suggested to test the validity of this hypothesis.